Nouvelles réflexions sur les instruments figurés dans les manuscrits du traité De fistula in ano de John Arderne

L’auteur pense que l’usage des instruments proposés par le chirurgien militaire anglais John Arderne pour traiter les fistules à l’anus n’est en rien explicite. Les divers manuscrits pourvus de dessins d’instruments et de protocoles opératoires soulèvent des problèmes d’interprétation quant à l’emploi précis de certains d’entre eux, en particulier le tendiculum. Le texte princeps n’est pas connu et nous sommes confrontés à des manuscrits en latin et en vieil anglais datant du XIVe et du XVe siècle. Il convient d’avoir à l’esprit l’intrication importante entre le texte et les dessins par les sigles utilisés pour les protocoles opératoires car John Arderne insiste beaucoup sur le rôle et la conception de son instrumentation. Ceci est souligné par « As it is painted ». La méthode de recherche historique et critique nous a poussés à scruter et comparer d’abord les plus vieux manuscrits de la fin du XIVe siècle puis ceux du XVe et d’y entrevoir certaines filiations. Nous voyons la transformation du graphisme des instruments au fur et à mesure du passage du temps. La beauté de certains manuscrits et de leurs figures n’est en rien un critère de valeur scientifique. Un manuscrit peu chatoyant mais complet comme le Mss sloane 3844 présente un intérêt majeur et cela se voit bien dans l’étude d’un appareil innovant comme le tendiculum dont l’emploi multiple prête à discussion. Parfois, une petite lumière instructive éclot de la lecture ou de la représentation d’un instrument dans un manuscrit plus tardif et même les erreurs sont sources d’une part de la recherche de la vérité, comme le montre encore l’étude du tendiculum ingénieux du Maître en chirurgie, John Arderne.The author believes that there has been insufficient explanation of the use of the instruments described by the medieval English Surgeon John Arderne, to treat fistula in ano. Examining the existing manuscripts, which describe the instruments and the operations, bring to light some problems of interpretation, particularly in relation to the tendiculum. The primary text is unknown and we have to use various texts in Latin and Old English from the 14th and 15th Centuries

Telomeres and Telomerase in Neuroblastoma

Telomeres are nucleoprotein structures located at the ends of linear chromosomes. In most human adult normal somatic cells, telomeres shorten after each cellular division. This shortening ultimately leads to senescence and/or apoptosis. By contrast, in most cancer cells, telomerase activation compensates this loss and confers to these cells their infinite cell proliferation potential. Neuroblastoma (NBL) is a malignant tumor of the peripheral sympathetic nervous system and the most frequent extracranial solid tumor of childhood. NBLs are remarkably heterogeneous both at the levels of biology, genetic and clinical courses. Indeed, some of NBLs can regress spontaneously or after a mild treatment, while others are in the high-risk category with poor prognosis. The molecular bases underlying this heterogeneity are poorly understood. MYCN (V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma-derived Homolog) amplification, recognized as strongly associated with unfavorable patient outcome, is found in only 40% of the high-risk disease, indicating the involvement of other mechanisms. Recent observations suggest that telomerase expression and telomere dysfunctions may be one critical step in NBL development. This review provides recent insights on telomeres/telomerase regulation in NBL. Because of their involvement in the tumor cell biology, telomere and telomerase are currently at the core of new drug development

The epigenetic regulator RINF (CXXC5) maintains SMAD7 expression in human immature erythroid cells and sustains red blood cells expansion

The gene CXXC5, encoding a Retinoid-Inducible Nuclear Factor (RINF), is located within a region at 5q31.2 commonly deleted in myelodysplastic syndrome (MDS) and adult acute myeloid leukemia (AML). RINF may act as an epigenetic regulator and has been proposed as a tumor suppressor in hematopoietic malignancies. However, functional studies in normal hematopoiesis are lacking, and its mechanism of action is unknow. Here, we evaluated the consequences of RINF silencing on cytokineinduced erythroid differentiation of human primary CD34+ progenitors. We found that RINF is expressed in immature erythroid cells and that RINF-knockdown accelerated erythropoietin-driven maturation, leading to a significant reduction (~45%) in the number of red blood cells (RBCs), without affecting cell viability. The phenotype induced by RINF-silencing was TGFβ-dependent and mediated by SMAD7, a TGFβ- signaling inhibitor. RINF upregulates SMAD7 expression by direct binding to its promoter and we found a close correlation between RINF and SMAD7 mRNA levels both in CD34+ cells isolated from bone marrow of healthy donors and MDS patients with del(5q). Importantly, RINF knockdown attenuated SMAD7 expression in primary cells and ectopic SMAD7 expression was sufficient to prevent the RINF knockdowndependent erythroid phenotype. Finally, RINF silencing affects 5’-hydroxymethylation of human erythroblasts, in agreement with its recently described role as a Tet2- anchoring platform in mouse. Altogether, our data bring insight into how the epigenetic factor RINF, as a transcriptional regulator of SMAD7, may fine-tune cell sensitivity to TGFβ superfamily cytokines and thus play an important role in both normal and pathological erythropoiesis

Neural network-based emulation of interstellar medium models

The interpretation of observations of atomic and molecular tracers in the galactic and extragalactic interstellar medium (ISM) requires comparisons with state-of-the-art astrophysical models to infer some physical conditions. Usually, ISM models are too time-consuming for such inference procedures, as they call for numerous model evaluations. As a result, they are often replaced by an interpolation of a grid of precomputed models. We propose a new general method to derive faster, lighter, and more accurate approximations of the model from a grid of precomputed models. These emulators are defined with artificial neural networks (ANNs) designed and trained to address the specificities inherent in ISM models. Indeed, such models often predict many observables (e.g., line intensities) from just a few input physical parameters and can yield outliers due to numerical instabilities or physical bistabilities. We propose applying five strategies to address these characteristics: 1) an outlier removal procedure; 2) a clustering method that yields homogeneous subsets of lines that are simpler to predict with different ANNs; 3) a dimension reduction technique that enables to adequately size the network architecture; 4) the physical inputs are augmented with a polynomial transform to ease the learning of nonlinearities; and 5) a dense architecture to ease the learning of simple relations. We compare the proposed ANNs with standard classes of interpolation methods to emulate the Meudon PDR code, a representative ISM numerical model. Combinations of the proposed strategies outperform all interpolation methods by a factor of 2 on the average error, reaching 4.5% on the Meudon PDR code. These networks are also 1000 times faster than accurate interpolation methods and require ten to forty times less memory. This work will enable efficient inferences on wide-field multiline observations of the ISM

Les éditions de L’Histoire du roi Kaboul Ier et du marmiton Gauwain

Ségal Alain. Les éditions de L’Histoire du roi Kaboul Ier et du marmiton Gauwain. In: Les Cahiers Max Jacob, N°10, 2010. pp. 127-134